title: Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism.
abstract: The human APOBEC3 (A3A-A3H) locus encodes six cytidine deaminases that edit single-stranded DNA, the result being DNA peppered with uridine. Although several cytidine deaminases are clearly restriction factors for retroviruses and hepadnaviruses, it is not known if APOBEC3 enzymes have roles outside of these settings. It is shown here that both human mitochondrial and nuclear DNA are vulnerable to somatic hypermutation by A3 deaminases, with APOBEC3A standing out among them. The degree of editing is much greater in patients lacking the uracil DNA-glycolyase gene, indicating that the observed levels of editing reflect a dynamic composed of A3 editing and DNA catabolism involving uracil DNA-glycolyase. Nonetheless, hyper- and lightly mutated sequences went hand in hand, raising the hypothesis that recurrent low-level mutation by APOBEC3A could catalyze the transition from a healthy to a cancer genome.
authors.affiliation: Institut Pasteur, Molecular Retrovirology Unit, Centre National de la Recherche Scientifique URA3015, 75724 Paris cedex 15, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Suspène
authors.forename: Marie-Ming
authors.initials: MM
authors.lastname: Aynaud
authors.forename: Denise
authors.initials: D
authors.lastname: Guétard
authors.forename: Michel
authors.initials: M
authors.lastname: Henry
authors.forename: Grace
authors.initials: G
authors.lastname: Eckhoff
authors.forename: Agnès
authors.initials: A
authors.lastname: Marchio
authors.forename: Pascal
authors.initials: P
authors.lastname: Pineau
authors.forename: Anne
authors.initials: A
authors.lastname: Dejean
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vartanian
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
mesh_terms: D000071478:APOBEC Deaminases; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D006367:HeLa Cells; D015613:Hepadnaviridae / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D051981:Uracil-DNA Glycosidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D051981:Uracil-DNA Glycosidase; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase